Untreated chronic strongyloidiasis can predispose to Strongyloides hyperinfection syndrome (SHS) and disseminated strongyloidiasis, especially in the setting of immunosuppression [8]. SHS occurs through a process of accelerated autoinfection of the parasite with an increased number of larvae in the gastrointestinal tract and lungs. With disseminated strongyloidiasis, there is subsequent migration of larvae to organs outside the typical pulmonary autoinfection cycle, such as the liver, heart, and brain [9]. A common complication of this is Gram-negative bacteraemia secondary to translocation of enteric bacteria accompanying larval invasion of the gut wall [6]. SHS confers a mortality rate of greater than 85% [10].

Corticosteroid use is the most important risk factor for development of SHS in high-income countries [8]. This association is hypothesized to be through the acute suppression of cytokines such as IL-5, eosinophil and lymphocyte proliferation and activation, and by directly increasing the fertility of adult female worms [11]. This risk is independent of the duration, dose, and route of corticosteroid administration [8]. Courses of corticosteroids as short as six days and with a dose of oral prednisone as low as 20 mg per day have been shown to result in SHS [6]. Other immunomodulating medications such as methotrexate have also demonstrated association with accelerating Strongyloides’ autoinfection cycle [12]. In our case, the pre-existing immunosuppression for rheumatoid arthritis with methotrexate, hydroxychloroquine, and sulfasalazine likely contributed to his symptoms leading up to presentation and primed his condition for the rapid progression of larvae dissemination after receiving corticosteroids.

Our case highlights the diagnostic and management challenges of strongyloidiasis and the importance of epidemiologic history in determining risk. Patients often present with non-specific symptoms, which may lead to diagnostic and treatment delays. Furthermore, stool examination for parasites detects less than 30% of the cases given irregular shedding, with higher sensitivities during increased parasite burden and excretion [13]. Serologic testing is the most sensitive diagnostic test, but false negatives occur frequently. False negatives occur even more commonly in patients on immunosuppression. False positives can also occur with other helminth infections.

Epidemiologic risk factors for strongyloidiasis include birth, residence in, or travel to Sub-Saharan Africa, South America, the Caribbean, Southeast Asia, and Oceania. Even though strongyloidiasis is endemic to these tropical and subtropical regions, there is increasing prevalence in traditionally non-endemic countries due to travel and migration. Infection may occur with even very short periods of exposure, especially in people residing in rural settings or frequenting beach areas [10, 14]. There are several case reports describing strongyloidiasis acquired by short-term travellers, even as short as a week, and clinicians must assess this epidemiologic risk [14, 15]. Also, because strongyloidiasis is a lifelong infection until treated, any travel, regardless of remoteness, is relevant for risk assessment [14,15,16] Given the high mortality associated with SHS, clinicians must have a high index of suspicion for untreated chronic strongyloidiasis in any patient with epidemiologic risk. A combination of risk assessment along with serologic and stool testing is needed prior to starting immunosuppression [13].

Universal serologic testing for S. stercoralis in patients with COVID-19 who have epidemiologic risk has been recommended by some authors [17]. However, there are limitations to serological testing as the sensitivity of serology is lower in those who are immunocompromised or on immunosuppressive medications [18]. Empiric treatment with ivermectin in at-risk patients is a reasonable strategy due to the delayed turn-around time for serologic testing and the time-sensitive nature of starting corticosteroid therapy for COVID-19 disease [19]. A similar strategy has been used previously in at-risk patients undergoing immunosuppression, as research demonstrates that the cost-effectiveness of empiric treatment is non-inferior to a “test and treat” approach [10]. Another strategy is to initiate early treatment for strongyloidiasis in new refugees/migrants at the time of migration/arrival, but policies and practices vary in different geographic locations and clinicians should not rely on the assumption that Strongyloides risk has been addressed on migration/arrival and must do their own individual risk assessment for Strongyloides, especially if initiating any immunosuppressive medications [20].

Clinical risk factors associated with progression of strongyloidiasis and development of SHS include HTLV-1/2 infection, treatment with glucocorticoid or immunomodulatory agents, organ transplantation and hematologic malignancies [10]. The presence of unexplained serum eosinophilia in a patient who was born in or has travelled to an endemic region should also prompt investigation for strongyloidiasis. Peripheral eosinophilia, however, is not a sensitive marker for Strongyloides infection, and therefore its absence does not rule out infection [13].

Given the risk of SHS, consideration should be given for treating those at high risk of strongyloidiasis empirically if they will be initiated on corticosteroids or other immunosuppressives [10, 21]. While there have been attempts to study the optimal dosing of oral Ivermectin, the studies have been underpowered, have not directly studied all dosing regimens, or have a large number of participants lost to follow up [21, 22]. Two doses of oral Ivermectin 200 ug/kg/d usually separated by 2 weeks is the current practice standard. For people who are already immunosuppressed, additional doses of Ivermectin may be required. Additionally, albendazole 400 mg orally twice daily should be considered in patients with suspected SHS or disseminated strongyloidiasis, as well as empiric antibiotics with activity against gram-negative bacteria [23]. For those unable to tolerate ivermectin orally or suspected to have decreased gut absorption, it should be administered subcutaneously or intramuscularly [24]. In patients from West or Central Africa, special attention must be made to prevent the precipitation of ivermectin associated encephalopathy in the context of concurrent untreated loiasis [10].